Pentameric viral ion channels : from structure to function
A family of small polypeptides in many virus types associate to form oligomers and have channel activity. These proteins have been referred to as viroporins or virochannels and are increasingly recognized as important virulence factors and potential drug targets. In this review, we focus on two of t...
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| Format: | Journal Article |
| Language: | English |
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2015
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| Online Access: | https://hdl.handle.net/10356/107200 http://hdl.handle.net/10220/25365 |
| _version_ | 1811690186556309504 |
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| author | Surya, Wahyu Li, Yan Torres, Jaume |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Surya, Wahyu Li, Yan Torres, Jaume |
| author_sort | Surya, Wahyu |
| collection | NTU |
| description | A family of small polypeptides in many virus types associate to form oligomers and have channel activity. These proteins have been referred to as viroporins or virochannels and are increasingly recognized as important virulence factors and potential drug targets. In this review, we focus on two of the viroporins that have been studied in more detail from a structural and functional point of view. One is the 76-residue envelope (E) protein found in coronaviruses (CoVs) that causes the severe acute respiratory syndrome (SARS). The other is the 65-residue small hydrophobic (SH) protein found in a paramyxovirus, the respiratory syncytial virus (RSV). RSV SH and SARS-CoV E proteins are short polypeptides with a single transmembrane domain. In both cases, the presence of the viroporin has a protective effect on cells, preventing early apoptosis, but it leads to increased virulence in infected animal models. Both viroporins form homopentameric oligomers that show channel activity with no or low selectivity. The role of channel activity is still unclear, but associations have been made to facilitation of the egress of the virus by modification of the secretory pathway, and contributions to inflammation. SARS-CoV E protein has a cytoplasmically oriented C-terminus and a lumenal N-terminus, whereas the opposite orientation is found in RSV SH protein. Despite this opposite topology, nuclear magnetic resonance (NMR)-based structural models of these two channels show a similar champagne flute shape, with the wider opening facing the cytoplasmic side. Good channel inhibitors are lacking, but those found seem to have a preference for the narrow end of the channel. Availability of good inhibitors will help reveal the specific role of these channels in the life cycle of these viruses. |
| first_indexed | 2024-10-01T06:00:00Z |
| format | Journal Article |
| id | ntu-10356/107200 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:00:00Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/1072002023-02-28T17:03:05Z Pentameric viral ion channels : from structure to function Surya, Wahyu Li, Yan Torres, Jaume School of Biological Sciences DRNTU::Science::Biological sciences A family of small polypeptides in many virus types associate to form oligomers and have channel activity. These proteins have been referred to as viroporins or virochannels and are increasingly recognized as important virulence factors and potential drug targets. In this review, we focus on two of the viroporins that have been studied in more detail from a structural and functional point of view. One is the 76-residue envelope (E) protein found in coronaviruses (CoVs) that causes the severe acute respiratory syndrome (SARS). The other is the 65-residue small hydrophobic (SH) protein found in a paramyxovirus, the respiratory syncytial virus (RSV). RSV SH and SARS-CoV E proteins are short polypeptides with a single transmembrane domain. In both cases, the presence of the viroporin has a protective effect on cells, preventing early apoptosis, but it leads to increased virulence in infected animal models. Both viroporins form homopentameric oligomers that show channel activity with no or low selectivity. The role of channel activity is still unclear, but associations have been made to facilitation of the egress of the virus by modification of the secretory pathway, and contributions to inflammation. SARS-CoV E protein has a cytoplasmically oriented C-terminus and a lumenal N-terminus, whereas the opposite orientation is found in RSV SH protein. Despite this opposite topology, nuclear magnetic resonance (NMR)-based structural models of these two channels show a similar champagne flute shape, with the wider opening facing the cytoplasmic side. Good channel inhibitors are lacking, but those found seem to have a preference for the narrow end of the channel. Availability of good inhibitors will help reveal the specific role of these channels in the life cycle of these viruses. Published version 2015-04-10T07:53:18Z 2019-12-06T22:26:34Z 2015-04-10T07:53:18Z 2019-12-06T22:26:34Z 2015 2015 Journal Article Surya, W., Li, Y., & Torres, J. (2014). Pentameric viral ion channels : from structure to function. Journal of receptor, ligand and channel research, 2015(8), 9-18. 1178-699X https://hdl.handle.net/10356/107200 http://hdl.handle.net/10220/25365 10.2147/JRLCR.S36064 en Journal of receptor, ligand and channel research © 2015 Surya et al.This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Surya, Wahyu Li, Yan Torres, Jaume Pentameric viral ion channels : from structure to function |
| title | Pentameric viral ion channels : from structure to function |
| title_full | Pentameric viral ion channels : from structure to function |
| title_fullStr | Pentameric viral ion channels : from structure to function |
| title_full_unstemmed | Pentameric viral ion channels : from structure to function |
| title_short | Pentameric viral ion channels : from structure to function |
| title_sort | pentameric viral ion channels from structure to function |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/107200 http://hdl.handle.net/10220/25365 |
| work_keys_str_mv | AT suryawahyu pentamericviralionchannelsfromstructuretofunction AT liyan pentamericviralionchannelsfromstructuretofunction AT torresjaume pentamericviralionchannelsfromstructuretofunction |